摘要
目的:研究右美托咪定对心肌肥厚模型家兔心律失常及心肌组织中钙离子-钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)表达的影响。方法:将家兔随机分为假手术组,模型组,右美托咪定低、中、高剂量组(10、25、50μg/kg),CaMKⅡ抑制剂KN-93组(10mg/kg)和右美托咪定高剂量+KN-93组(50μg/kg+10 mg/kg),每组10只。除假手术组外,其余各组家兔均采用腹主动脉缩窄术复制心肌肥厚模型。术后,各给药组家兔静脉注射相应剂量的右美托咪定或/和腹腔注射KN-93,假手术组和模型组家兔静脉注射等体积生理盐水,隔天给药1次,连续给药8周。末次给药后,采用程序性刺激诱发室性心律失常,记录各组家兔早期后除极(EAD)和尖端扭转型室性心动过速(Tdp)的诱发率,检测左室射血分数(LVEF)和左心室缩短分数(FS),记录离体楔形心肌组织QT间期、跨室壁复极离散度(TDR)和内、外膜心肌细胞跨膜动作电位复极90%时程(APD90),测量并计算心脏质量/体质量比值(HW/BW)以及左心室壁厚度(LVT),检测心肌细胞横截面积以及心肌组织中心房钠尿肽(ANP)和脑钠肽(BNP)mRNA以及CaMKⅡ、磷酸化CaMKⅡ(p-CaMKⅡ)蛋白的相对表达量。结果:与假手术组比较,模型组家兔EAD、Tdp诱发率和HW/BW、LVT以及心肌组织中ANP、BNP m RNA的相对表达量和CaMKⅡ、p-CaMKⅡ蛋白的相对表达量均显著升高,LVEF、FS均显著降低,QT间期和内、外膜心肌APD90均显著延长,TDR显著增加,心肌细胞横截面积显著增大(P<0.05)。与模型组比较,各给药组家兔EAD、Tdp诱发率和HW/BW(右美托咪定低剂量组除外)、LVT(右美托咪定低剂量组除外)以及心肌组织中ANP mRNA(右美托咪定低剂量组除外)、BNP mRNA(右美托咪定低剂量组除外)的相对表达量和CaMKⅡ、p-CaMKⅡ蛋白的相对表达量均显著降低,LVEF(右美托咪定低剂量组除外)、FS(右美托咪定低剂量组除外)均显著升高,QT间期和内、外膜心肌APD90均显著
OBJECTIVE:To study the effects of dexmedetomidine on ventricular arrhythmia in myocardial hypertrophy model rabbits and the expression of calcium ion/calmodulin-dependent protein kinaseⅡ(CaMKⅡ)in myocardial tissue of rabbits.METHODS:The rabbits were randomly divided into sham operation group,model group,dexmedetomidine low-dose,medium-dose and high-dose groups(10,25,50μg/kg),CaMKⅡinhibitor KN-93 group(10 mg/kg),high-dose of dexmedetomidine+KN-93 group(50μg/kg+10 mg/kg),with 10 rabbits in each group.Except for the sham operation group,other groups received abdominal aortic coarctation to induce myocardial hypertrophy model.After surgery,administration groups were given relevant dose of dexmedetomidine or/and intraperitoneal injection of KN-93;sham operation group and model group were given constant volume of normal saline intravenously,once every other day,for consecutive 8 weeks.After last medication,programmed stimulation was used to induce ventricular arrhythmia.The induction rate of early posterior depolarization(EAD)and tip torsion type ventricular tachycardia(Tdp)were recorded.Left ventricular ejection fraction(LVEF)and left ventricular shortener fraction(FS)were measured.QT interval,transventricular wall repolarization dispersion(TDR)and transmembrane 90%action potential duration(APD90)of endocardial and epicardial cardiomyocytes in wedge-shaped myocardium were recorded.The ratio of heart weight to body weight(HW/BW)and the thickness of left ventricular wall(LVT)were measured and calculated.The cross-sectional area of cardiomyocytes,m RNA expression of ANP and BNP as well as protein expression of Ca MKⅡand p-Ca MKⅡin myocardial tissue was measured.RESULTS:Compared with sham operation group,the induction rate of EAD and Tdp,HW/BM,LVT,mRNA expression of ANP and BNP and protein relative expression of CaMKⅡand p-CaMKⅡin cardiac tissue were all increased significantly,while LVEF and FS were decreased significantly;QT interval,APD90 of endocardial and epicardial cardiomyocytes were all prolonged s
作者
刘旭东
赵亮
曹雪峰
胡杰
LIU Xudong;ZHAO Liang;CAO Xuefeng;HU Jie(Dept.of Anesthesiology,Chengde Central Hospital,Hebei Chengde 067024,China;Dept.of Pharmacology,Chengde Medical College,Hebei Chengde 067050,China;Dept.of Anesthesiology,the Affiliated Hospital of Chengde Medical College,Hebei Chengde 067020,China)
出处
《中国药房》
CAS
北大核心
2021年第18期2209-2217,共9页
China Pharmacy
基金
国家自然科学基金资助项目(No.81700310)
承德市科学技术研究与发展计划项目(No.201904A099)。
